CPT® Code 81320

Official Description

PLCG2 (phospholipase C gamma 2) (eg, chronic lymphocytic leukemia) gene analysis, common variants (eg, R665W, S707F, L845F)

Common Language Description

Molecular genetic testing is a critical procedure used to identify specific mutations within the PLCG2 (phospholipase C gamma 2) gene, particularly those common variants associated with chronic lymphocytic leukemia (CLL). The PLCG2 gene is situated on the long (q) arm of chromosome 16 at position 23.3 (16q23.3) and encodes a transmembrane signaling enzyme that plays a vital role in cellular communication. This enzyme utilizes calcium to facilitate the conversion of inositol trisphosphate (IP3) and diacylglycerol (DAG), which are essential for transporting growth factor and immune system receptors across cell membranes. The specific mutations identified through this testing include R665W, S707F, and L845F, all of which are single amino acid substitution mutations that lead to a gain of function in the enzyme's activity. The R665W mutation, occurring on exon 19 of the SH domain, replaces arginine with tryptophan. The S707F mutation, found on exon 20 of the SH domain, substitutes serine with phenylalanine. Lastly, the L845F mutation, located on exon 24 of the PH domain, involves the substitution of leucine with phenylalanine. These mutations are significant as they are linked to resistance against commonly prescribed CLL treatments such as ibrutinib and acalabrutinib. The testing for these variants may be conducted prior to the initiation of treatment and/or during the course of treatment to inform therapeutic decisions. The CPT® Code 81320 specifically reports the analysis of the PLCG2 gene to identify these common functional variants by comparing gene segments to ascertain similarities or differences and to elucidate relationships among them.

1. Indications

The PLCG2 gene analysis is indicated for patients diagnosed with chronic lymphocytic leukemia (CLL) to identify specific genetic mutations that may influence treatment decisions. The following conditions warrant this genetic testing:

Chronic Lymphocytic Leukemia (CLL) - Patients with a confirmed diagnosis of CLL may undergo testing to detect common variant mutations in the PLCG2 gene, which are associated with the disease and its treatment response.
Resistance to Treatment - Testing may be indicated for patients who exhibit resistance to standard therapies such as ibrutinib and acalabrutinib, as the identified mutations (R665W, S707F, L845F) are known to confer resistance to these drugs.
Pre-Treatment Assessment - Genetic testing may be performed prior to initiating treatment to guide therapeutic choices and optimize patient management based on the presence of specific mutations.
Monitoring During Treatment - The analysis may also be conducted during treatment to assess the emergence of mutations that could affect ongoing therapy and patient outcomes.

2. Procedure

The procedure for conducting PLCG2 gene analysis involves several key steps to ensure accurate identification of the common variant mutations associated with chronic lymphocytic leukemia. The following procedural steps are typically followed:

Step 1: Sample Collection - A biological sample, usually blood or bone marrow, is collected from the patient. This sample serves as the source of DNA for the genetic analysis.
Step 2: DNA Extraction - The DNA is extracted from the collected sample using standardized laboratory techniques. This step is crucial for obtaining high-quality DNA that will be analyzed for mutations.
Step 3: Amplification of Target Regions - Polymerase chain reaction (PCR) is employed to amplify the specific regions of the PLCG2 gene where the common variants (R665W, S707F, L845F) are located. This amplification is necessary to ensure that there is enough DNA for accurate analysis.
Step 4: Sequencing or Genotyping - The amplified DNA is then subjected to sequencing or genotyping methods to identify the presence of the specific mutations. This step involves comparing the patient's DNA sequence to a reference sequence to detect any variations.
Step 5: Data Analysis - The results are analyzed to determine the presence of the common variants. Bioinformatics tools may be used to interpret the data and assess the significance of any identified mutations.
Step 6: Reporting Results - A comprehensive report is generated, detailing the findings of the genetic analysis, including the presence or absence of the R665W, S707F, and L845F mutations. This report is then provided to the healthcare provider for clinical decision-making.

3. Post-Procedure

After the PLCG2 gene analysis is completed, the healthcare provider will review the results with the patient. If mutations associated with resistance to treatment are identified, the provider may consider alternative therapeutic options or adjust the current treatment plan accordingly. It is essential for the patient to have a follow-up appointment to discuss the implications of the test results and any necessary changes in their treatment strategy. Additionally, ongoing monitoring may be recommended to assess the patient's response to therapy and to detect any new mutations that may arise during treatment. The overall goal of post-procedure care is to ensure that the patient receives the most effective treatment based on their genetic profile.

Short Descr	PLCG2 GENE COMMON VARIANTS
Medium Descr	PLCG2 GENE ANALYSIS COMMON VARIANTS
Long Descr	PLCG2 (phospholipase C gamma 2) (eg, chronic lymphocytic leukemia) gene analysis, common variants (eg, R665W, S707F, L845F)
Status Code	Statutory Exclusion (from MPFS, may be paid under other methodologies)
Global Days	XXX - Global Concept Does Not Apply
PC/TC Indicator (26, TC)	9 - Not Applicable
Multiple Procedures (51)	9 - Concept does not apply.
Bilateral Surgery (50)	9 - Concept does not apply.
Physician Supervisions	09 - Concept does not apply.
Assistant Surgeon (80, 82)	9 - Concept does not apply.
Co-Surgeons (62)	9 - Concept does not apply.
Team Surgery (66)	9 - Concept does not apply.
Diagnostic Imaging Family	99 - Concept Does Not Apply
CLIA Waived (QW)	No
APC Status Indicator	Service Paid under Fee Schedule or Payment System other than OPPS
Type of Service (TOS)	5 - Diagnostic Laboratory
Berenson-Eggers TOS (BETOS)	none
MUE	1

90	Reference (outside) laboratory: when laboratory procedures are performed by a party other than the treating or reporting physician or other qualified health care professional, the procedure may be identified by adding modifier 90 to the usual procedure number.
XS	Separate structure, a service that is distinct because it was performed on a separate organ/structure
GW	Service not related to the hospice patient's terminal condition
XU	Unusual non-overlapping service, the use of a service that is distinct because it does not overlap usual components of the main service
59	Distinct procedural service: under certain circumstances, it may be necessary to indicate that a procedure or service was distinct or independent from other non-e/m services performed on the same day. modifier 59 is used to identify procedures/services, other than e/m services, that are not normally reported together, but are appropriate under the circumstances. documentation must support a different session, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same individual. however, when another already established modifier is appropriate it should be used rather than modifier 59. only if no more descriptive modifier is available, and the use of modifier 59 best explains the circumstances, should modifier 59 be used. note: modifier 59 should not be appended to an e/m service. to report a separate and distinct e/m service with a non-e/m service performed on the same date, see modifier 25.
91	Repeat clinical diagnostic laboratory test: in the course of treatment of the patient, it may be necessary to repeat the same laboratory test on the same day to obtain subsequent (multiple) test results. under these circumstances, the laboratory test performed can be identified by its usual procedure number and the addition of modifier 91. note: this modifier may not be used when tests are rerun to confirm initial results; due to testing problems with specimens or equipment; or for any other reason when a normal, one-time, reportable result is all that is required. this modifier may not be used when other code(s) describe a series of test results (eg, glucose tolerance tests, evocative/suppression testing). this modifier may only be used for laboratory test(s) performed more than once on the same day on the same patient.
GV	Attending physician not employed or paid under arrangement by the patient's hospice provider